Association of D-dimer with Plaque Characteristics and Plasma Biomarkers of Oxidation-Specific Epitopes in Stable Subjects with Coronary Artery Disease

Abstract

D-dimer has emerged as a biomarker of cardiovascular event risk, yet pathophysiological factors associated with plasma D-dimer levels in stable coronary artery disease (CAD) subjects are poorly understood. In 106 stable CAD subjects undergoing intravascular ultrasound with virtual histology (IVUS-VH), we measured D-dimer, lipoprotein(a) (Lp(a)), plasminogen, biomarkers reflecting oxidation-specific epitopes (OSE) such as oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), OxPL on plasminogen (OxPL-PLG), and autoantibodies to phosphorylcholine-BSA [PC-BSA] and a malondialdehyde [MDA] mimotope. In univariate analysis, D-dimer was positively associated with Lp(a), OxPL-apoB, OxPL-PLG, and coronary artery calcium, and inversely associated with autoantibodies to OSE and plaque fibrosis. D-dimer levels > 500 ng/ml also showed positive association with plaque necrosis. After multivariate analysis, D-dimer remained significantly associated with Lp(a) and plaque calcium. While further studies are needed, results provide evidence that plasma D-dimer levels are associated with levels of OxPLs and IVUS-VH indices linked to plaque erosion and rupture.

D-dimer as a thrombus biomarker for predicting 2-year mortality after percutaneous coronary intervention

“…D-dimer levels reflect increased coagulation and fibrinolytic activity. 1 Elevation of D-dimer levels is associated with some pathological processes, including thrombosis, 1 plaque necrosis, 20 infection, 18 and cancer metastasis, 5 which may make it an independent risk marker for all-cause mortality and cardiovascular mortality.…”

Hospital mortality in acute coronary syndrome: adjustment of GRACE score by D-dimer enables a more accurate prediction in a prospective cohort study

“…Pathophysiological factors associated with plasma D-dimer levels in coronary artery disease patients were studied. In stable coronary artery disease subjects, high D-dimer had a significant association with plaque necrosis, lipoprotein (a) and plaque calcium [6]. D-dimer level also independently predicted no-reflow in STEMI patients with primary PCI [7, 8].…”

“…It is also a biomarker of coagulation state and the form of thrombosis [5]. Elevated D-dimer was associated with vulnerable plaque [6], no-reflow after PCI [7, 8] and a larger myocardial injury assessed by cardiac magnetic resonance (CMR) [9]. Many studies also confirmed the association between higher D-dimer and the increased long-term mortality in patients with stable coronary artery disease [10, 11], ACS [12] and ST-segment elevation myocardial infarction (STEMI) [13, 14].…”

Lipoproteins as targets and markers of lipoxidation

“…For example, a reclassification of cardiovascular event in subjects from the Bruneck study followed over 15 years, which reported that the highest tertile of OxPL/ApoB was associated with higher risk of cardiovascular disease and stroke [136]. A study of stable subjects with coronary artery disease showed that oxidized phospholipids on ApoB-100 (oxPL-apoB) and plasminogen (oxPL-PLG) in plasma correlated positively with D-dimer, an end product of fibrin degradation that indicates a pro-thrombotic state [137]. The relationship of oxPLs in Lp(a) to calcific aortic valve disease (CAVD) has also been investigated in the Copenhagen General population study, and showed that oxPL-apoB, oxPL-apo(a) and lipoprotein(a) levels all associated with risk of CAVD, suggesting that they may be causal risk factors for the condition [138].…”